The present invention provides novel compositions of matter. In particular, the present invention provides novel derivatives of the leukotrienes. Most particularly, the present invention provides novel derivatives of leukotrienes A and C.
The leukotrienes are a class of unsaturated fatty acid compounds which are derived from arachadonic acid by the action of lipoxygenase. See, e.g., Samuelsson, Trends in Pharmacological Sciences, 5:227 (1980); and Samuelsson, et al., Annu. Rev. Biochem. 47:997-1029 (1978). This pathway is depicted in Chart D. For a discussion of leukotriene nomenclature, see Samuelsson, et al., Prostaglandins, 19:645 (1980).
The leukotrienes have been discovered as potent constrictors of human bronchi. That is, certain leukotrienes are mediators of the action of slow-reacting substance of anaphylaxis (SRS-A). See, e.g., Dahlen, Nature, 288:484 (1980). These compounds are therefore important mediators of bronchoconstriction in humans.
The role of leukotrienes as agonists in immediate hypersensitivity and other pathological conditions has led to research into inhibitors of leukotriene biosynthesis and leukotriene antagonists. See, e.g., Corey, et al., Tet. Lett. 21:4243 (1980).
Surprisingly and unexpectedly the leukotriene derivatives disclosed herein have been found to be leukotriene antagonists and inhibitors of SRS-A formation. They are also thromboxane synthetase inhibitors.